Neuromuscular disease, chronic obstructive pulmonary disease (COPD) and obese hypoventilation patients often suffer from chronic respiratory failure. Said patients need regular treatment of their respiratory failure at home. Hypoxemic patients are treated by oxygen therapy (mostly without ventilator support), while treatment by Invasive Ventilation (IV) or Non Invasive Ventilation (NIV) with environmental air helps bringing the high carbon dioxide blood gas level of hypercapnic patients back to an acceptable level. The efficacy of the ventilation is checked by measuring the base-line and the trends in the arterial oxygen and carbon dioxide levels during nocturnal ventilation.
Arterial blood gas measurements form the golden standard. Before starting ventilation treatment at home, patients stay at the hospital to optimize ventilator settings and monitor arterial blood gas values. Depending on disease severity and stability, patients have to return more or less regularly to the hospital for checks. A respiratory nurse can also visit the patient at home to check the ventilator and to install equipment that enables non-invasive monitoring of blood gas partial pressures. At home, blood gas levels are monitored typically during a night and data are stored together with ventilator and respiratory data for later analysis at the hospital.
The state of the art in non-invasive blood oxygenation monitoring, is by measuring the arterial oxygen saturation, which relates to the partial oxygen pressure via the oxygen dissociation curve. Pulse oximetry (SpO2) is an optical method for non-invasive monitoring of arterial oxygen saturation in a patient and has become one of the most commonly used technologies in clinical practice. Pulse oximetry is a reasonably low cost technology and is easy to use. It is the preferred method for blood oxygenation monitoring at home.
The state of the art in non-invasive monitoring of the partial pressure of CO2 is by means of capnography or by transcutaneous CO2 (PtcCO2) monitoring. For intubated patients with a healthy lung the end-tidal CO2 (etCO2) value obtained by capnography offers a good indication of the arterial CO2 value. However, in case of non-invasive ventilation where air leaks between mask and face are usually present and the patients have severe respiratory diseases capnography is often not a reliable method. In most hospitals a combination is used of capnography for trend monitoring and analysis of an arterial blood sample to obtain an occasional accurate value.
Transcutaneous CO2 monitoring is not disrupted by air-leaks and respiratory diseases but requires trained personal to obtain reliable values and shows some inaccuracy due to variation in skin properties among adults. At home non-invasive CO2 blood gas monitoring is less frequently used than oximetry despite its high relevance for patients receiving ventilation.
The current transcutaneous CO2 sensor is based on a 40 year old concept of                a thermostatically controlled heater to increase blood perfusion and gas-permeability of the skin,        a fluid layer between skin and sensor membrane,        a gas-permeable membrane covering the sensor,        an electrolyte solution between membrane and sensor,        a sensor comprising an electrochemical pH sensor and reference electrode, and        an algorithm to compensate for temperature effects and skin metabolism.        
To derive the transcutaneous CO2 value from the measured—cutaneous—partial CO2 pressure, the difference between the sensor temperature and the arterial blood temperature of 37° C. has to be taken into account. Furthermore, an offset is subtracted from the measured value to compensate for the skin metabolism that varies somewhat with skin temperature.
Arterialization of the skin is essential for transcutaneous blood gas measurements to obtain a transcutaneous value that is close to the arterial CO2 blood gas level. The existing technology is based on arterialization by heating the skin below the sensor surface. In currently available transcutaneous systems the minimal sensor temperature for arterialization is 42° C. and the required heating power is ˜500 mW at maximum, mainly needed to compensate for the cooling effect of the blood flow.
In order to come up with a low-cost, non-invasive PaCO2 monitoring solution chemo optical sensing technology has been applied for transcutaneous CO2 detection.
FIG. 1 shows a typical principle of operation of a chemo optical sensor for transcutaneous CO2 detection. A sensor spot with a gas-permeable layer 13 (e.g. silicone membrane+TiO2), which is transparent to gas and reflective to light, is in contact with a patient's skin. The gas-permeable layer 13 facilitates gas diffusion (e.g. CO2) from the skin into a sensing layer 12 (e.g. silicone membrane+reference dye+indicator dye), which is transparent to gas, incorporates an indicator dye which is pH sensitive and a reference dye which is insensitive to gas concentrations. An optically transparent carrier 11 covers the sensing layer 12. The optically transparent carrier 11 may have a thickness d1 of about 0.2 mm, the sensing layer 12 may have a thickness d2 of about 0.1 mm, and the gas-permeable layer 13 may have a thickness d3 of about 0.1 mm. A diameter of the sensor spot x1 may be about 5 mm.
A predetermined radiation 100 is irradiated onto the sensor spot and in particular the sensing layer 12. The predetermined radiation 100 may have a wavelength of about 470 nm (blue-green LED). The indicator and reference dye emit radiation 200 in response to an excitation caused by the predetermined radiation 100. The characteristics of said radiation 200 (optical response) depend on the amount of CO2 gas that is present in/has diffused into the sensing layer 12. Accordingly, by analyzing the radiation 200, a gas concentration in the sensing layer and thus, in the skin, can be determined.
At first sight the properties of these sensor spots look unmistakably advantageous for the design of a transcutaneous sensor device for the home market in terms of dynamic range, pre-calibration/compensation for deviating temperature, stability and cost-effectiveness.
In order to dissolve the polar indicator dye into the hydrophobic polymer sensing layer a lipophilic phase transfer agent is added, which lipophilic phase transfer agent also serves as an internal buffer to provide water for production of carbonic acid. However, the water content in the sensor spots is known (and experimentally validated) to display a strong cross-sensitivity towards osmotic differences, which makes the control of the osmotic properties of the surrounding fluid between tight constraints inevitable. This is well feasible in certain application fields of these sensor spots but is cumbersome or impossible for others. In theory, sensitivity to osmolality can be reduced at the cost of a trade-off on the shelf-life and response time of the sensor spots.
Furthermore, temperature affects the excited states and chemical balance inside the dye and shifts the detection curve. Luminescence changes due to variations in the lightpath are effectively suppressed by using a Dual-Lifetime Referencing technology. By balancing the temperature sensitivity and photo-bleaching of the indicator- and reference-dye also these effects can be suppressed. In the end the sensor signal can be (partly) compensated by a-priori knowledge of the temperature coefficients.
As mentioned above, said CO2 sensor spots are designed for in-fluid measurements where temperature and osmotic pressure is uniform. When shifting from this (intended) application towards a transcutaneous sensor an additional problem arises, namely:
A temperature gradient across the membrane of the sensor spot occurs, in particular in a direction perpendicular to the sensing plane, causing relevant gradient-dependent signal drift, most likely caused by fluid pumping and related osmotic changes. Generally speaking this phenomenon is known as thermal creep or thermal transpiration and was first utilized by M. H. Knudsen (1910) for gas pumping. It is also related to thermo phoresis and thermo diffusion. It is a new and highly relevant problem in chemo-optical sensor spots applied for transcutaneous sensing, as thermal gradients are inevitably present.
WO 2012/045047 discloses a non-invasive transcutaneous blood gas sensing system for determining information on arterial blood gas in a mammal, comprising a combined diffusion and measurement chamber comprising at least one gas permeable surface adapted to allow transcutaneous diffusion of analytes from a mammal when the gas permeable surface is in contact with the mammal, at least one optical chemical sensor positioned in the combined diffusion and measurement chamber that is adapted to chemically interact and/or physically react with a respective analyte, and an optoelectronic system positioned outside the combined diffusion and measurement chamber for remotely detecting the chemical interaction and/or the physical interaction of the at least one optical chemical sensor.